Project Summary Environmental enteropathy (EE), a diffuse villous atrophy of the small bowel characterized by T cell infiltration, is common among the developing world's children. The impact of this disorder is immense. EE increases intestinal permeability, which leads to nutrient and medication malabsorption, stunting, and decreased oral vaccine efficacy. The cause of EE is unknown. It has been long hypothesized that a microbial etiology underlies this disorder, based on observations that expatriates from high-income countries develop EE in endemic areas and that this lesion resolves on repatriation to North America or Europe. However, specific bacterial or parasitic etiologies have not been reproducibly or strongly associated with EE. Remarkably, the potential viral etiology of EE remains completely unexplored. Here, we will determine if viruses are associated with the development of EE. To do so, we will use an unbiased metagenomic approach to define the enteric viromes in a unique longitudinal cohort of 489 Malawian children with detailed outcome data and ~2,500 stools. This proposal will define the enteric viral populations in these children, and confirm or refute an association between viruses and EE. If we establish an association between viral infection and EE, our work will alter the approach to this widespread, overlooked, and highly consequential disorder of the digestive tracts of children worldwide.